Miren Altuna1,2,3, Rosa Larumbe4,5, María Victoria Zelaya6, Sira Moreno7, Virginia García-Solaesa7, Maite Mendioroz4,5, María Antonia Ramos7, María Elena Erro8,9. 1. Sant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau-Universitat Autònoma de Barcelona, Barcelona, Spain. maltuna@cita-alzheimer.org. 2. Centre of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain. maltuna@cita-alzheimer.org. 3. CITA-Alzheimer Foundation, Donostia-San Sebastián, Spain. maltuna@cita-alzheimer.org. 4. Department of Neurology, Hospital Universitario de Navarra, Pamplona, Spain. 5. Neuroepigenetics Laboratory-Navarrabiomed, Hospital Universitario de Navarra, Universidad Pública de Navarra (UPNA), IdiSNA (Navarra Institute for Health Research), Pamplona, Spain. 6. Department of Pathological Anatomy, Hospital Universitario de Navarra, Pamplona, Spain. 7. Department of Genetics, Hospital Universitario de Navarra, Pamplona, Spain. 8. Department of Neurology, Hospital Universitario de Navarra, Pamplona, Spain. elena.erro.aguirre@navarra.es. 9. Neuroepigenetics Laboratory-Navarrabiomed, Hospital Universitario de Navarra, Universidad Pública de Navarra (UPNA), IdiSNA (Navarra Institute for Health Research), Pamplona, Spain. elena.erro.aguirre@navarra.es.
Abstract
INTRODUCTION: Autosomal dominant Alzheimer's disease (ADAD) due to presenilin 1 (PSEN1) mutation can induce atypical neurological symptoms such as movement disorders and epileptic seizures in the context of early-onset progressive cognitive impairment. METHODS: This study includes the anatomoclinical description of three patients of two generations of the same family with movement disorders and progressive cognitive impairment. All were evaluated by trained neurologists, underwent protocolized neuropsychological evaluation, and were assessed by structural (magnetic resonance) and functional (SPECT, PET-18FDG, or PET-18F-Florbetapir) brain imaging tests. A molecular genetic study was performed for all patients, and post-mortem confirmatory anatomopathological evaluation for one of them. RESULTS: The three female patients had an age of onset of symptoms of 38-51 years. All developed progressive multidomain cognitive impairment, paraparesis, and dysarthria, two with ophthalmoparesis and one with untriggered epileptic seizures since early stages. Bilateral cortical fronto-parietal atrophy and global cortical hypoperfusion or posterior bilateral hypometabolism were detected. PET-18F-Florbetapir, when performed, was positive for amyloid cortical deposit. The molecular genetic study confirmed the PSEN1 mutation c.869-2 A>G. Postmortem study of one of them confirmed Alzheimer's disease anatomopathological features with classic cotton wool plaques (CWP), including coexistence of amyloid angiopathy and Lewy body co-pathology. DISCUSSION: The phenotype of ADAD due to PSEN1 mutations is very heterogeneous between and across the same family. Family history assessment should include information not only about cognitive decline, but also about movement disorders and untriggered epileptic seizures. Further studies are needed to identify genetic or epigenetic factors that determine phenotypic diversity in this disease.
INTRODUCTION: Autosomal dominant Alzheimer's disease (ADAD) due to presenilin 1 (PSEN1) mutation can induce atypical neurological symptoms such as movement disorders and epileptic seizures in the context of early-onset progressive cognitive impairment. METHODS: This study includes the anatomoclinical description of three patients of two generations of the same family with movement disorders and progressive cognitive impairment. All were evaluated by trained neurologists, underwent protocolized neuropsychological evaluation, and were assessed by structural (magnetic resonance) and functional (SPECT, PET-18FDG, or PET-18F-Florbetapir) brain imaging tests. A molecular genetic study was performed for all patients, and post-mortem confirmatory anatomopathological evaluation for one of them. RESULTS: The three female patients had an age of onset of symptoms of 38-51 years. All developed progressive multidomain cognitive impairment, paraparesis, and dysarthria, two with ophthalmoparesis and one with untriggered epileptic seizures since early stages. Bilateral cortical fronto-parietal atrophy and global cortical hypoperfusion or posterior bilateral hypometabolism were detected. PET-18F-Florbetapir, when performed, was positive for amyloid cortical deposit. The molecular genetic study confirmed the PSEN1 mutation c.869-2 A>G. Postmortem study of one of them confirmed Alzheimer's disease anatomopathological features with classic cotton wool plaques (CWP), including coexistence of amyloid angiopathy and Lewy body co-pathology. DISCUSSION: The phenotype of ADAD due to PSEN1 mutations is very heterogeneous between and across the same family. Family history assessment should include information not only about cognitive decline, but also about movement disorders and untriggered epileptic seizures. Further studies are needed to identify genetic or epigenetic factors that determine phenotypic diversity in this disease.
Authors: Sigrun Roeber; Felix Müller-Sarnowski; Julia Kress; Dieter Edbauer; Tanja Kuhlmann; Frank Tüttelmann; Christoph Schindler; Pia Winter; Thomas Arzberger; Ulrich Müller; Adrian Danek; Hans A Kretzschmar Journal: J Neural Transm (Vienna) Date: 2015-09-08 Impact factor: 3.575
Authors: David S Knopman; Helene Amieva; Ronald C Petersen; Gäel Chételat; David M Holtzman; Bradley T Hyman; Ralph A Nixon; David T Jones Journal: Nat Rev Dis Primers Date: 2021-05-13 Impact factor: 52.329
Authors: I Uttner; J Kirchheiner; H Tumani; F M Mottaghy; E Lebedeva; E Ozer; A C Ludolph; R Huber; C A F von Arnim Journal: Eur J Neurol Date: 2009-11-12 Impact factor: 6.089